Reduction in the amplitude of shortening and Ca(2+) transient by phlorizin and quercetin-3-O-glucoside in ventricular myocytes from streptozotocin-induced diabetic rats.

Abstract

Diabetes mellitus is the leading cause of cardiovascular morbidity and mortality. Phlorizin (PHLOR) and quercetin-3-O-glucoside (QUER-3-G) are two natural compounds reported to have antidiabetic properties by inhibiting sodium/glucose transporters. Their effects on ventricular myocyte shortening and intracellular Ca(2+) in streptozotocin (STZ)-induced diabetic rats were investigated. Video edge detection and fluorescence photometry were used to measure ventricular myocyte shortening and intracellular Ca(2+), respectively. Blood glucose in STZ rats was 4-fold higher (469.64+/-22.23 mg/dl, n=14) than in Controls (104.06+/-3.36 mg/dl, n=16). The amplitude of shortening was reduced by PHLOR in STZ (84.76+/-2.91 %, n=20) and Control (83.72+/-2.65 %, n=23) myocytes, and by QUER-3-G in STZ (79.12+/-2.28 %, n=20) and Control (76.69+/-1.92 %, n=30) myocytes. The amplitude of intracellular Ca(2+) was also reduced by PHLOR in STZ (82.37+/-3.16 %, n=16) and Control (73.94+/-5.22 %, n=21) myocytes, and by QUER-3-G in STZ (73.62+/-5.83 %, n=18) and Control (78.32+/-3.54 %, n=41) myocytes. Myofilament sensitivity to Ca(2+) was not significantly altered by PHLOR; however, it was reduced by QUER-3-G modestly in STZ myocytes and significantly in Controls. PHLOR and QUER-3-G did not significantly alter sarcoplasmic reticulum Ca(2+) in STZ or Control myocytes. Altered mechanisms of Ca(2+) transport partly underlie PHLOR and QUER-3-G negative inotropic effects in ventricular myocytes from STZ and Control rats.